The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Congestive heart failure (CHF) is a fatal disease with a 5-year mortality rate that rivals the most deadly malignancies. For example, in the Framingham Heart Study, median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Moreover, a person age 40 or older has a one-in-five lifetime chance of developing congestive heart failure. Heart failure typically develops after other conditions have damaged the heart. Coronary artery disease, and in particular myocardial infarction, is the most common form of heart disease and the most common cause of heart failure.
The appropriate treatments given to patients suffering from heart failure are diverse. For example, diuretics are often given to reduce the increased fluid load characteristic of heart failure; Angiotensin-converting enzyme (ACE) inhibitors are a class of vasodilator used to lower blood pressure, improve blood flow and decrease the workload on the heart; Angiotensin II receptor blockers (ARBs) have many of the same benefits as ACE inhibitors; and Beta blockers may reduce signs and symptoms of heart failure and improve heart function.
In recent years, natriuretic peptide measurement has dramatically changed the diagnosis and management of cardiac diseases, including heart failure and the acute coronary syndromes. In particular, B-type natriuretic peptide (BNP, human precursor Swiss-Prot P16860), various related polypeptides arising from the common precursor proBNP (such as NT-proBNP), and proBNP itself have been used to diagnose heart failure, determine its severity, and estimate prognosis. In addition, BNP and its related polypeptides have been demonstrated to provide diagnostic and prognostic information in unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction.
BNP and its related peptides are correlated with other measures of cardiac status such as New York Heart Association classification. However, many patients with chronic stable or asymptomatic heart failure will have natriuretic peptide levels in the normal diagnostic range (e.g., BNP levels less than about 100 pg/mL; NT-proBNP levels less than about 400 pg/mL). There is a trade-off in selecting diagnostic cutoff levels for these markers, because lowering the cutoff decreases the false-negative rate (i.e., increased sensitivity and fewer missed diagnoses) but increases the false-positive rate (i.e., decreased specificity and more incorrect diagnoses).
There remains a need in the art for markers which can be used for diagnosis and risk stratification of patients having or suspected of having congestive heart failure.